Chromatin and Epigenetics Lab, Department of Biotechnology, University of Kashmir, Srinagar, Jammu, Kashmir 190006, India.
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Mutat Res Rev Mutat Res. 2016 Apr-Jun;768:46-52. doi: 10.1016/j.mrrev.2016.03.005. Epub 2016 Mar 31.
Dot1/DOT1L (disruptor of telomeric silencing-1) is an evolutionarily conserved histone methyltransferase that methylates lysine 79 located within the globular domain of histone H3. Dot1 was initially identified by a genetic screen as a disruptor of telomeric silencing in Saccharomyces cerevisiae; further, it is the only known non-SET domain containing histone methyltransferase. Methylation of H3K79 is involved in the regulation of telomeric silencing, cellular development, cell-cycle checkpoint, DNA repair, and regulation of transcription. hDot1L-mediated H3K79 methylation appears to have a crucial role in transformation as well as disease progression in leukemias involving several oncogenic fusion proteins. This review summarizes the multiple functions of Dot1/hDOT1L in a range of cellular processes.
Dot1/DOT1L(端粒沉默破坏因子 1)是一种进化上保守的组蛋白甲基转移酶,它甲基化组蛋白 H3 球状结构域中赖氨酸 79 位的残基。Dot1 最初是通过遗传筛选在酿酒酵母中被鉴定为端粒沉默破坏因子;此外,它是唯一已知的非 SET 结构域含有组蛋白甲基转移酶。H3K79 的甲基化参与端粒沉默、细胞发育、细胞周期检查点、DNA 修复和转录调控的调节。hDot1L 介导的 H3K79 甲基化似乎在涉及多种致癌融合蛋白的白血病的转化以及疾病进展中起着关键作用。这篇综述总结了 Dot1/hDOT1L 在多种细胞过程中的多种功能。